Mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus: therapeutic and evolutionary implications
Mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus: therapeutic and evolutionary implications
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DOI：
10.1111/mmi.13167
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发表时间：
2015-12-01
影响因子：
3.6
通讯作者：
Wagener, Johannes
中科院分区：
文献类型：
--
作者：
Neubauer, Michael;Zhu, Zhaojun;Wagener, Johannes
真核细胞内的线粒体不断融合和分裂。这种现象被称为线粒体动力学，对线粒体功能和完整性至关重要。我们进行了全面的分析线粒体动力学的致病性霉菌烟曲霉。相应的突变体的表型表征揭示了线粒体基因组的维护和模具的生存能力的线粒体融合的一般必要性。令人惊讶的是，线粒体菱形蛋白酶Pcp 1及其加工产物s-Mgm 1在酵母中对融合至关重要，而在A.烟熏。相比之下，线粒体分裂突变体显示出显著降低的生长和孢子形成速率以及增加的热敏感性。然而，确保了线粒体对新形成的分生孢子的可靠遗传。引人注目的是，线粒体分裂突变体显示出显着的和生长条件依赖性的唑类耐药性的增加。分裂突变体中融合的平行破坏部分挽救了生长和孢子形成缺陷，并进一步增加了唑类抗性表型。两者合计，我们的研究结果表明，一个新兴的线粒体菱形蛋白酶功能的线粒体融合，线粒体融合机制作为抗真菌药物的目标和线粒体动力学的参与唑类药物敏感性的适用性。
Mitochondria within eukaryotic cells continuously fuse and divide. This phenomenon is called mitochondrial dynamics and crucial for mitochondrial function and integrity. We performed a comprehensive analysis of mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus. Phenotypic characterization of respective mutants revealed the general essentiality of mitochondrial fusion for mitochondrial genome maintenance and the mold's viability. Surprisingly, it turned out that the mitochondrial rhomboid protease Pcp1 and its processing product, s-Mgm, 1 which are crucial for fusion in yeast, are dispensable for fusion, mtDNA maintenance and viability in A. fumigatus. In contrast, mitochondrial fission mutants show drastically reduced growth and sporulation rates and increased heat susceptibility. However, reliable inheritance of mitochondria to newly formed conidia is ensured. Strikingly, mitochondrial fission mutants show a significant and growth condition-dependent increase in azole resistance. Parallel disruption of fusion in a fission mutant partially rescues growth and sporulation defects and further increases the azole resistance phenotype. Taken together, our results indicate an emerging dispensability of the mitochondrial rhomboid protease function in mitochondrial fusion, the suitability of mitochondrial fusion machinery as antifungal target and the involvement of mitochondrial dynamics in azole susceptibility.